More than 500,000 infants are born prematurely annually and 50-70 percent have later impairments requiring specialized services. Costs associated with preterm birth in the U.S. were at least $26.2 billion in 2005. A recent Institute of Medicine report recommends long term outcome studies into young adulthood for preterm infants to determine the extent of recovery, if any, and to monitor them for the onset of disease. In this competing renewal, we respond to this recommendation and propose an eighth study at age 23 of a unique sample of 213 infants grouped by prematurity and perinatal morbidity with a full term control group. We have retained 92 percent of the sample since birth and 97 percent since age 12. We now propose to examine the impact of prematurity, medical history and environments on achievements and deficits during young adulthood. Raised by the Developmental Origins Theory, we will investigate whether the impact of prematurity on poor health and early disease onset could be explained by alteration in hypothalamic-pituitary-adrenal axis (HPA) function. The specific aims are to: (1) Determine effects of prematurity and risk and protective processes on adult outcomes of health, functional performance, emotional intelligence, executive function, and work competence at age 23; (2) Determine the developmental trajectories for growth, neurological morbidities, and psychological problems from birth to age 23 and estimate the effects of cumulative risk and protective processes; (3) Examine the relationship of HPA function and prematurity and its impact on adult outcomes of cardiovascular function, functional performance, emotional intelligence, executive function, and work competence at age 23. Data will to be collected during home and laboratory visits using standardized questionnaires, interviews and objective performance based assessments. Biomarkers are integrated and include blood chemistry, pulmonary function testing, cardiopulmonary response to exercise and metabolic functioning, and HPA function by salivary cortisol. Our analysis approach will use mixed models which enable determination of whether the covariates predict outcome across time, if the relationship changes over time, and if within-subject changes in outcome are predicted by changes in a covariate. Given the state of the science, this prospective, 5-group longitudinal design will establish the extent of recovery from prematurity and the onset of disease during adulthood within a developmental framework characterized by risk and protection processes. When developmental trajectories from premature birth through early adulthood and factors that influence and impede them are understood, we will be better able to understand the etiology of long term outcomes to pinpoint the timing and content of preventative interventions. This project is designed to fulfill this goal. Formulating a science of prevention requires attention to complex interactions between infants and their contexts across periods of time. Thus, the project is closely aligned with the initiatives of Healthy People 2010, the IOM, and NINR. PUBLIC HEALTH RELEVANCE: More than 525,000 infants are born prematurely annually and 50 percent-70 percent have later impairments requiring specialized services. Costs associated with preterm birth in the United States were at least $26.2 billion in 2005 and expected to rise as more preterm infants survive. Understanding trajectories from premature birth through adulthood, and the processes that affect them, will enable professionals to make early identification of those at risk to more accurately pinpoint the timing and content of intervention.